Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue.
Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.
Samra
J S
JS
Oxford Lipid Metabolism Group, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, United Kingdom.
Clark
M L
ML
Humphreys
S M
SM
MacDonald
I A
IA
Bannister
P A
PA
Frayn
K N
KN
D020155:3-Hydroxybutyric Acid; D000005:Abdomen; D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004951:Esterification; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008066:Lipolysis / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D002787:Sterol Esterase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D014280:Triglycerides; D019344:Lactic Acid; D002787:Sterol Esterase; D008071:Lipoprotein Lipase; C007133:hydrocortisone hemisuccinate; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone